反应详情

温度

110 °C

A mixture of whole amount of 4-(3-chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-methylsulfinylpyrimidine (prepared in the above (5)), 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine 73 mg, triethylamine 0.083 ml and N,N-dimethylacetamide 4 ml is stirred at 110° C. for 4 hours. After cooling the reaction mixture is diluted with a 10% aqueous citric acid solution and washed with ethyl acetate. The organic layer is extracted with a 10% aqueous citric acid solution. The water layer is made basic with sodium hydrogen carbonate and extracted with ethyl acetate. The ethyl acetate layer is washed, dried and concentrated in vacuo. The residue is separated with silica gel chromatography (solvent; chloroform:methanol=100:1→50:1), and then crystallized from a mixture of ethyl acetate, methanol and isopropyl ether to give 4-(3-chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)pyrimidine as a colorless crystalline powder 20 mg.

1. temperatureAfter cooling the reaction mixture
2. washwashed with ethyl acetate
3. extractionThe organic layer is extracted with a 10% aqueous citric acid solution
4. extractionextracted with ethyl acetate
5. washThe ethyl acetate layer is washed
6. customdried
7. concentrationconcentrated in vacuo
8. customThe residue is separated with silica gel chromatography (solvent; chloroform:methanol=100:1→50:1)
9. customcrystallized from a mixture of ethyl acetate, methanol and isopropyl ether